Neuropsychiatric SLE: from animal model to human.

Animal models are a key element in disease research and treatment. In the field of neuropsychiatric lupus research, inbred, transgenic and disease-induced mice provide an opportunity to study the pathogenic routes of this multifactorial illness. In addition to achieving a better understanding of the immune mechanisms underlying the disease onset, supplementary metabolic and endocrine influences have been discovered and investigated. The ever-expanding knowledge about the pathologic events that occur at disease inception enables us to explore new drugs and therapeutic approaches further and to test them using the same animal models. Discovery of the molecular targets that constitute the pathogenic basis of the disease along with scientific advancements allow us to target these molecules with monoclonal antibodies and other specific approaches directly. This novel therapy, termed "targeted biological medication" is a promising endeavor towards producing drugs that are more effective and less toxic. Further work to discover additional molecular targets in lupus' pathogenic mechanism and to produce drugs that neutralize their activity is needed to provide patients with safe and efficient methods of controlling and treating the disease.

Advances in the Interpretation of Tomographic Images as an Early Detection Method of Oil Palm Affected by Basal Stem Rot in Colombia.

Basal stem rot, one of the most important diseases of oil palm in Southeast Asia, has also been identified in Colombia. The increase in disease incidence in the last decade has attracted the attention of producers and researchers. In the search for a procedure that allows for the early identification of diseased palm, Cenipalma evaluated the use of electrical impedance tomography to identify the different stages of development of basal stem rot. The tomograms were compared with transversal sections of healthy and diseased oil palm trees. Following Cenipalma's preliminary studies on early diagnosis of basal stem rot with tomography, the present study improved upon the technique by analyzing the tomograms of 209 diseased palm trees (confirmed by symptomatology), 346 asymptomatic palm trees, and 132 healthy palm trees. The minimum and maximum electric impedance values as well as the ratio between these values was recorded. The range of 1 to 95 Ω was used to represent the internal damage. The ratios averaged 5.1 for diseased, 1.9 for asymptomatic, and 1.5 for healthy palm trees. With the range and the ratio criteria established, it was possible to identify the disease in 100% of asymptomatic sampled palm trees. This study demonstrated that electrical impedance tomography is a powerful tool for early detection of basal stem rot, which can be used to establish an early disease management program.

Altered precipitation regime affects the function and composition of soil microbial communities on multiple time scales.

Climate change models predict that future precipitation patterns will entail lower-frequency but larger rainfall events, increasing the duration of dry soil conditions. Resulting shifts in microbial C cycling activity could affect soil C storage. Further, microbial response to rainfall events may be constrained by the physiological or nutrient limitation stress of extended drought periods; thus seasonal or multiannual precipitation regimes may influence microbial activity following soil wet-up. We quantified rainfall-driven dynamics of microbial processes that affect soil C loss and retention, and microbial community composition, in soils from a long-term (14-year) field experiment contrasting "Ambient" and "Altered" (extended intervals between rainfalls) precipitation regimes. We collected soil before, the day following, and five days following 2.5-cm rainfall events during both moist and dry periods (June and September 2011; soil water potential = -0.01 and -0.83 MPa, respectively), and measured microbial respiration, microbial biomass, organic matter decomposition potential (extracellular enzyme activities), and microbial community composition (phospholipid fatty acids). The equivalent rainfall events caused equivalent microbial respiration responses in both treatments. In contrast, microbial biomass was higher and increased after rainfall in the Altered treatment soils only, thus microbial C use efficiency (CUE) was higher in Altered than Ambient treatments (0.70 +/- 0.03 > 0.46 +/- 0.10). CUE was also higher in dry (September) soils. C-acquiring enzyme activities (beta-glucosidase, cellobiohydrolase, and phenol oxidase) increased after rainfall in moist (June), but not dry (September) soils. Both microbial biomass C:N ratios and fungal:bacterial ratios were higher at lower soil water contents, suggesting a functional and/or population-level shift in the microbiota at low soil water contents, and microbial community composition also differed following wet-up and between seasons and treatments. Overall, microbial activity may directly (C respiration) and indirectly (enzyme potential) reduce soil organic matter pools less in drier soils, and soil C sequestration potential (CUE) may be higher in soils with a history of extended dry periods between rainfall events. The implications include that soil C loss may be reduced or compensated for via different mechanisms at varying time scales, and that microbial taxa with better stress tolerance or growth efficiency may be associated with these functional shifts.

Presence and expression of the mating type locus in Paracoccidioides brasiliensis isolates.

Paracoccidioides brasiliensis has been classified in the phylum Ascomycota, order Onygenales, family Ajellomycetaceae, even in the absence of a known sexual cycle or mating system. The objective of this work was to determine the presence of the mating type locus in 71 P. brasiliensis isolates from various sources. A PCR assay using specific primers for the MAT 1 gene was developed and applied for the detection of such genes. Two heterothallic groups (MAT1-1 or MAT1-2) were recognized and, in some isolates, gene expression was confirmed indicating the existence of a basal gene expression. The distribution of two mating type loci in the studied population suggested that sexual reproduction might occur in P. brasiliensis. This finding points towards the possibility of applying a more precise definition of the concept of biological species to P. brasiliensis. Further studies should be conducted to confirm the sexual capacity of this fungus and its implications among phylogenetic species and geographical distribution.

Near-infrared spectroscopy as an index of brain and tissue oxygenation.

Continuous real-time monitoring of the adequacy of cerebral perfusion can provide important therapeutic information in a variety of clinical settings. The current clinical availability of several non-invasive near-infrared spectroscopy (NIRS)-based cerebral oximetry devices represents a potentially important development for the detection of cerebral ischaemia. In addition, a number of preliminary studies have reported on the application of cerebral oximetry sensors to other tissue beds including splanchnic, renal, and spinal cord. This review provides a synopsis of the mode of operation, current limitations and confounders, clinical applications, and potential future uses of such NIRS devices.

Early childhood caries, salivary and microbiological aspects among 3- to 4-year-old children in Cali, Colombia.

AIM: To investigate the presence of early childhood caries (ECC) in relation to plaque index, colony-forming units of Streptococcus mutans (S. mutans) and Lactobacillus spp., pH and salivary buffer capacity in day-care pre-schooler's aged 3-4 years old in Cali, Colombia, 2016. METHODS: Caries prevalence was determined in 124 children using the International Caries Detection and Assessment System and plaque index. In addition, a non-stimulated saliva sample was obtained to determine its pH, and buffer capacity. RESULTS: 55.65% of the children had ECC. The mean decayed-missing-filled teeth index was 2.94 ± 4.26. The absence or presence of ECC, compared to the median plaque index showed statistically significant differences (p < 0.05). There was not an association between ECC and S. mutans, Lactobacillus spp. colonies, pH and buffer capacity of saliva. CONCLUSIONS: This study reported association between ECC and the increasing amount of bacterial plaque. Other important biological risk factors were not associated with ECC. Regular tooth cleaning can be the most important public health measure to control ECC in day-care children.

Cross-reactivity between annexin A2 and Beta-2-glycoprotein I in animal models of antiphospholipid syndrome.

Antiphospholipid syndrome (APS) affects coagulation and the brain by autoimmune mechanisms. The major antigen in APS is beta-2-glycoprotein I (ß2-GPI) is known to complex with annexin A2 (ANXA2), and antibodies to ANXA2 have been described in APS. We measured these antibodies in mice with experimental APS (eAPS) induced by immunization with ß2-GPI. Sera of these mice reacted significantly with recombinant ANXA2 by enzyme-linked immunosorbent assay (ELISA) and the eAPS mice had significantly high levels of immunoglobulin G (IgG) in the brain by immunoblot assays compared to adjuvant immunized controls. Immunoprecipitation performed by mixing eAPS brain tissue with protein-G beads resulted in identification of two autoantigens unique to the eAPS group, one of which was ANXA2. In order to study more directly and methodically the specific role of anti-ANXA2 antibodies in APS, we immunized mice with ß2-GPI which contained no ANXA2 or with ANXA2 and measured antibodies to these proteins. Levels of antibodies to ANXA2 measured by ELISA were 0.72 ± 0.007 arbitrary units (a.u), 0.24 ± 0.03 and 0.02 ± 0.01 a.u for sera from ANXA2, ß2-GPI and control mice, respectively (p < 0.0001 and p = 0.037 for the comparison of the ANXA2 and ß2-GPI groups to the controls). Purified IgG from ß2-GPI sera did not show cross-binding with ANXA2. Antibodies to ß2-GPI and phospholipids were found in the ß2-GPI immunized group only. The present study suggests an immune response to the ß2-GPI-ANXA2 complex in eAPS and provides a novel ANXA2 immunization model which will serve to study the role of ANXA2 antibodies in of APS.

Antibodies from patients with dengue viral infection mediate cellular cytotoxicity.

Acute and late convalescent sera (collected at day 5 of disease onset and 1 year later) from dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) laboratory confirmed cases, were tested for antibody-dependent cell-mediated cytotoxicity (ADCC) activity using dengue 1 (DENV-1) or dengue 2 (DENV-2) infected cells as target. All patients experienced their first dengue virus (DENV) infection 20 years before. ADCC activity was detected in acute sera from DHF/DSS but not in sera from DF patients. However, 1 year after illness, ADCC activity was observed in all cases. This preliminary report represents one of the few studies of ADCC in dengue patients and suggests that ADCC could be implicated in dengue pathogenesis.

Magnesium for acute traumatic brain injury.

BACKGROUND: Acute traumatic brain injury is a leading cause of death and disability in young adults. Magnesium had been considered as a potential therapeutic tool because of its activity on NMDA-receptors, calcium channels and neuron membranes. Animals studies have indicated a beneficial effect of magnesium on outcome after brain injury, but its efficacy in humans is unknown. OBJECTIVES: To quantify the effect of magnesium administration on mortality and morbidity in patients with acute traumatic brain injury. SEARCH STRATEGY: We searched the Cochrane Injuries Group's specialised register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, National Research Register, Current Controlled Trials, SIGLE, LILACS, Zetoc. The searches were conducted in July 2005. SELECTION CRITERIA: We included all randomized controlled trials comparing any magnesium salt with no magnesium or with placebo, in patients following acute traumatic brain injury. DATA COLLECTION AND ANALYSIS: Two authors independently screened search results and assessed the full texts of potentially relevant studies for inclusion. Data were extracted and methodological quality was examined. MAIN RESULTS: Three studies met the inclusion criteria, one of which is an ongoing study. Two studies were included in the analysis. No data on mortality were available. For Glasgow Outcome Score at six months the pooled WMD = 0.55 (95% CI -0.15 to 1.26), P = 0.12. AUTHORS' CONCLUSIONS: There is currently no evidence to support the use of magnesium salts in patients with acute traumatic brain injury.

Muc4/sialomucin complex, an intramembrane modulator of ErbB2/HER2/Neu, potentiates primary tumor growth and suppresses apoptosis in a xenotransplanted tumor.

Overexpression of the membrane mucin MUC4/Sialomucin complex (SMC) has been observed during malignant progression of mammary tumors in both humans and rats, suggesting that deregulation of MUC4/SMC expression might facilitate development of these malignancies. As previously reported, overexpression of SMC results in suppression of both cell adhesion and immune killing of tumor cells. SMC also acts as a ligand for ErbB2/Neu, modulating phosphorylation of the receptor tyrosine kinase in the presence and absence of heregulin. The present studies investigated the effect of Muc4/SMC up-regulation on primary tumor growth using a tetracycline-inducible SMC expression system in a xenotransplanted tumor model. SMC up-regulation provoked rapid growth of transfected A375 melanoma in nude mice. Up-regulation of SMC, however, did not significantly increase proliferation of A375 cells in vitro. Instead, a strong suppression of apoptosis was observed in situ in SMC-overexpressing tumors. These data suggest that Muc4/SMC expression promotes tumor growth in vivo at least in part via suppression of tumor cell apoptosis. Importantly, reduction of apoptosis was also observed in vitro, indicating that anti-apoptotic effect of SMC is independent of tumor-host interactions. These findings strongly suggest that SMC up-regulation alters intracellular signaling to favor cell survival, providing for the first time evidence for the regulation of programmed cell death by a gene of the MUC family.

Human skin keratinocytes modified by a Friend-derived retroviral vector: a functional approach.

The goal of this study was to test the efficiency and possible functional effects of a Friend Leukemia derived retrovirus vector (FOCH29-NeoR) on cultured human keratinocytes, obtained from skin biopsy samples. The keratinocytes were grown and infected with filtered Friend vector supernatant. After one or two doses of infection, one duplicate of the culture was submitted to selection with G418; the other one was utilized for DNA extraction and PCR modification detection. Transduction efficiency was 46.66 percent and 47.22 percent for one and two doses of infection respectively (range 100 to 15 %). Colony Forming Efficiency (CFE) assays were done with Rodhamine-B staining in nonselected modified cultures and negative controls. There was no difference in CFE (% CFE= 10.74+/-6.53 negative control vs % CFE= 9.22+/-5.45 with one dose, and % CFE= 10.03+/-5.74 with two doses of infection). Nevertheless, the cell-cycle analysis done by Propidium Iodade (PI) incorporation and colchicine-arrest assays in nonselected transduced and nontransduced cells show that transduced keratinocytes have a longer time to enter G2. As far as we know, this is the first report of retroviral transduction-induced changes in the cell cycle done on human keratinocytes. This observation is very important because retroviral vectors of genes, such as platelet derived growth factor (PDGF) or vascular endothelial growth factor (VEGF), are expected to facilitate the implementation of these modified cultures for tissue grafting and skin substitute development and potentiate the effectiveness of the grafts.

Evaluación del dolor y la distensión abdominal según el agente insuflante (CO 2 frente al aire) en una unidad de endoscopia digestiva avanzada de Manizales, Colombia / Comparison of abdominal pain and distention due to insufflation with CO 2 versus insufflation with air in an advanced digestive endoscopy unit in Manizales, Colombia

Resumen Objetivo: comparar la magnitud del dolor y el perímetro abdominal; la incidencia del dolor y la distensión abdominal, y las complicaciones según el agente insuflante utilizado. Pacientes y método: estudio prospectivo analítico de cohorte. Se recolectaron datos de 43 colangiopancreatografías retrógradas endoscópicas (CPRE) y 20 colonoscopias insufladas con dióxido de carbono (CO2); para cada una se buscó un examen control con aire ambiente. En total, se sumaron 86 CPRE y 40 colonoscopias. Además, se realizó una caracterización clínica, un análisis bivariado y multivariado. Resultados: el procedimiento más doloroso fue la colonoscopia; sin embargo, el 60 % de los pacientes de colonoscopia, y el 70 % de aquellos de CPRE, no presentaron dolor 15 minutos después de haber despertado luego del examen. Asimismo, no se hallaron diferencias estadísticamente significativas según la indicación del examen, la presencia o intensidad de dolor al momento del procedimiento, la edad, el sexo o el diagnóstico. El riesgo relativo (RR) de dolor inmediato fue 4,8 veces superior, cuando la insuflación se realizó con aire en vez de CO2 (RR = 4,8; intervalo de confianza [IC], 95 %: 2,3 a 9,2; p <0,001). Entre tanto, el riesgo de distensión abdominal en el grupo con aire fue 2,6 veces superior, en comparación con el grupo insuflado con CO2 (RR = 2,6; IC, 95 %: 1,8 a 3,9; p <0,001). El CO2 redujo la probabilidad y la magnitud de la distensión abdominal y de los dolores inmediatos, posteriores a la colonoscopia o a la CPRE. No hubo complicaciones en ninguno de los 126 pacientes. Conclusiones: el dolor y la distensión abdominal se presentan con menor frecuencia e intensidad cuando se usa CO2 como agente insuflante. Ninguno de los procedimientos presentó complicaciones mayores.

Abstract Objective: This study compares the incidence of abdominal pain and distension, the magnitude of pain, abdominal perimeter, and related complications related to two different insufflating agents. Patients and Method: Prospective analytical cohort study. Data were collected from 43 performances of endoscopic retrograde cholangiopancreatography (ERCPs) and 20 colonoscopies in which patients were insufflated with CO2. A control examination using ambient air for insufflation was performed for each patient. In total, 86 ERCPs and 40 colonoscopies were performed. The study includes clinical characterizations, bivariate analysis and multivariate analysis. Results: The most painful procedure was colonoscopy, but 60% of colonoscopy patients and 70% of ERCP patients had no pain 15 minutes after waking up following their examinations. No statistically significant differences related to reasons for examination, presence or intensity of pain at the time of the procedure, age, sex or diagnosis were found. The relative risk (RR) of immediate pain is 4.8 times higher when insufflation is done with air instead of CO2 (RR = 4.8; 95% CI: 2.3 to 9.2; p <0.001). The risk of abdominal distension in the air group was 2.6 times higher than that of the group insufflated with CO2 (RR = 2.6; 95% CI: 1.8 to 3.9; p <0.001). CO2 reduces the likelihood and extent of abdominal distension and immediate post colonoscopy or ERCP pain. There were no complications in any of the 126 patients. Conclusions: Abdominal pain and bloating occur less frequently and less intensely when CO2 is used as an insufflating agent. None of the procedures presented major complications.

Residual pulmonary abnormalities in adult patients with chronic paracoccidioidomycosis: prolonged follow-up after itraconazole therapy.

Itraconazole effectively controls active paracoccidioidomycosis but appears not to hinder lung fibrosis. Clinical records and chest radiographs from 47 itraconazole-treated patients with prolonged posttherapy follow-up (mean follow-up period, 5.6 years) were analyzed; the radiographs were interpreted following pneumoconiosis standards that consider the lungs as 6 fields and grade damage according to the number of fields involved. Infiltrative lesions were observed at diagnosis in 93.6% of the patients. Fibrosis was observed in 31.8% of the patients at diagnosis and had not cleared at the end of the observation period in any of these patients. Fibrosis also developed de novo in 11 patients (25%), so that by the end of the follow-up period it was seen in 53.2% of patients overall. Fibrosis correlated with severity of infiltrates at diagnosis: fibrosis was present in 83% of patients with very severe infiltration and in 12.5% of patients with minor infiltration. Among patients with severe infiltration, fibrosis was present in 30%; this increased (to 75%) when bullae were concomitantly present at diagnosis. Prompt initiation of treatment is necessary to avoid the development of fibrosis.

Treatment of paracoccidioidomycosis with ketoconazole: a three-year experience.

The results of ketoconazole therapy in 38 patients with active paracoccidioidomycosis are described. Treatment consisted of a 200 mg tablet a day for 6 months. Evaluation was accomplished by means of a scoring system and the results were as follows: none of the patients worsened during therapy, one was found to be unchanged, five had minor improvement, 330 had major improvement, and there was complete resolution of the pretherapy conditions in 13. These findings plus the lack of toxicity of the drug and the facility for oral administration, make of ketoconazole a first line drug for the treatment of paracoccidioidomycosis.

Post-therapy status of paracoccidioidomycosis treated with ketoconazole.

Twenty-four paracoccidioidomycosis patients who completed a course of therapy with ketoconazole were followed for 12 months after treatment, and 10 of these patients were followed for 24 months. Only two of these patients relapsed; the remaining continued in remission. There were no fatalities. Immunologic tests showed decreased antibody activity and increased skin test reactivity to paracoccidioidin in comparison with the results obtained at the end of therapy. These findings indicate that ketoconazole therapy has improved the prognosis of patients with paracoccidioidomycosis.

Childhood mental disorders in primary health care: results of observations in four developing countries. A report from the WHO collaborative Study on Strategies for Extending Mental Health Care.

To ascertain the frequency of mental disorders in Sudan, Philippines, India, and Columbia, 925 children attending primary health care facilities were studied. Rates of between 12% and 29% were found in the four study areas. The range of mental disorders diagnosed was similar to the encountered in industrialized countries. The research procedure involved a two-stage screening in which a ten-item "reporting questionnaire" constituted the first stage. The study has shown that mental disorders are common among children attending primary health care facilities in four developing countries and that accompanying adults (usually the mothers) readily recognize and report common psychologic and behavioral symptoms when these are solicited by means of a simple set of questions. Despite this, the primary health workers themselves recognized only between 10% and 22% of the cases of mental disorder. The result have been used to design appropriate brief training courses in childhood mental disorders for primary health workers in the countries participating in the study.

Production and localization of Muc4/sialomucin complex and its receptor tyrosine kinase ErbB2 in the rat lacrimal gland.

PURPOSE: To show the presence and forms of sialomucin complex (rat Muc4) and receptor tyrosine kinase ErbBs in the rat lacrimal gland and analyze for complexes of ErbB2 and its ligand Muc4. METHODS: Northern blot analyses were used to identify sialomucin complex/Muc4 (SMC/Muc4) mRNA in rat lacrimal gland. Immunoblot analyses were performed to detect SMC/Muc4 and ErbBs. Sequential immunoprecipitation and immunoblot analyses were used to differentiate membrane and soluble forms of the SMC/Muc4 transmembrane subunit ASGP-2. Methacarn-fixed, paraffin-embedded sections of lacrimal glands from female adult rats were immunocytochemically stained using antisera to SMC/Muc4 and ErbBs to determine their relative locations in the gland. Colocalization of SMC/Muc4 and ErbB2 was confirmed by confocal immunofluorescence. Sequential immunoprecipitation and immunoblot were performed to analyze complexes of the SMC/Muc4 and ErbB2 in the lacrimal tissue. RESULTS: Northern blot analyses of rat lacrimal glands, with a probe for SMC/Muc4, demonstrated the presence of a approximately 9-kb transcript, consistent with observations in other tissues. Similarly, immunoblot analyses with antibodies against both the transmembrane (ASGP-2) and mucin (ASGP-1) subunits showed the presence of the two SMC/Muc4 subunits in lysates from rat lacrimal gland. Significantly, two different forms of ASGP-2 were observed, a high-molecular-weight ( approximately 200-kDa) form and the more common 120- to 140-kDa form. Sequential immunoprecipitation and immunoblot analyses to differentiate membrane and soluble forms of SMC/Muc4 indicated that the high-molecular-weight form of ASGP-2 was predominantly associated with membranes, whereas the 120- to 140-kDa form was both membrane-associated and soluble. The lacrimal gland consists of acini connected by intercalated and interlobular ducts. Both acini and some intercalated ducts were stained by anti-ASGP-2 monoclonal antisera. Two patterns of acinar staining were observed: membrane staining at the borders of the epithelial cells and a granular staining within the cells. Staining of ductal surfaces with antibody to the cytoplasmic domain of ASGP-2 suggests that membrane SMC/Muc4 is being produced by the ductal cells and is not simply an adsorbed soluble product from the acinar cells. Immunoblot and immunocytochemical analyses demonstrated the presence of all four ErbBs, with ErbB2 showing the most widespread distribution, similar to that of SMC/Muc4. Immunofluorescence colocalization of membrane SMC/Muc4 and ErbB2 and coimmunoprecipitation of a complex of the two provided evidence of their association in membranes of lacrimal gland acinar cells. CONCLUSIONS: SMC/Muc4 is produced by the rat lacrimal gland as both membrane and soluble forms, specifically associated with both acinar and ductal cells. Because sialomucin complex is also present in the ocular tear film, the rat lacrimal gland represents a second source of this mucin for the tear film, in addition to the corneal and conjunctival epithelia. Moreover, the presence of a complex of SMC/Muc4 and the receptor tyrosine kinase ErbB2 in lacrimal tissue suggests that SMC/Muc4 acts as a ligand for the receptor and has functions in the lacrimal gland other than that of a mucin.

Disseminated histoplasmosis in children: the role of itraconazole therapy.

OBJECTIVES: To describe the clinical characteristics and laboratory diagnosis of seven children with disseminated histoplasmosis and evaluate the effectiveness of itraconazole therapy in this severe form of the mycosis as well as to determine the long term results of such treatment. METHODS: The diagnosis of histoplasmosis was based on the direct observation of Histoplasma capsulatum var. capsulatum and/or on the isolation of the fungus from pathologic materials; the results of the serologic tests were taken into consideration. Chest roentgenograms also contributed to the diagnosis. PATIENTS: The patients were seven rural children, five girls and two boys, ages 1 to 14 years (mean, 4.6), with a confirmed diagnosis of disseminated histoplasmosis and who had no underlying disease other than malnourishment. RESULTS: The seven children experienced a subacute febrile syndrome for 4 months accompanied by anorexia, weight loss and signs of reticuloendothelial involvement such as lymph node hypertrophy, hepatomegaly and/or splenomegaly. The lung revealed roentgenographic alterations consisting mainly of nodular infiltrates. All patients received itraconazole orally in a mean dosage of 7.2 mg/kg/day, for variable periods (3 to 12 months), depending on the individual response and the toxic effects of the medication. One of the patients who was improving after 1 month of treatment was taken from the hospital by his guardian against medical advice and died shortly afterward. The remaining six patients responded to the treatment with marked clinical improvement and showed negative cultures and decreases in anti-H. capsulatum antibody titers after 3 months of treatment. Only one patient, the youngest and most severely affected child, exhibited hepatotoxicity, which subsided when itraconazole was discontinued. Extended follow-up studies revealed no relapses. CONCLUSION: The results of this study indicate that itraconazole is effective for treatment of disseminated childhood histoplasmosis. More studies should be performed to determine the most appropriate dosage and the optimal duration of itraconazole treatment in children.

Knowledge and attitudes of primary health care personnel concerning mental health problems in developing countries: a follow-up study.

Within the context of a World Health Organization coordinated collaborative study health workers in six developing countries were assessed 18 months after their training for improvement in their knowledge and attitude towards mental health problems and their management. The approaches to training varied between study areas, but the degree of improvement following the training, was of equal magnitude in all countries. The training process has formalized the recognition by the health workers that treatment of mental health problems is an integral part of their work.

Treatment of chromoblastomycosis with itraconazole.

The results of long-term itraconazole therapy in 10 patients with active chromoblastomycosis due to F. pedrosoi were reported. Therapy consisted of 100 or 200 mg/day of itraconazole, the length of therapy depending on the patient's response (12 to 24 months). This new triazole proved effective in reducing the number, size, and severity of the lesions in nine of the patients. Those patients with minor involvement profited more from therapy and were cured; patients with moderate involvement achieved either minor or major improvement. In most cases, signs and symptoms began to improve after 6 months of therapy. Mycological tests (in which tissue samples were treated with potassium hydroxide and cultured) became negative in six patients, but the fungus was eradicated in only three patients. Itraconazole produced no side effects. In spite of the need for long-term therapy, this new azole derivative effectively controls the disease.